基于甜味受体的玉竹治疗阴虚证“补而不腻”作用机理研究

补阴药味甘，具有滋补、滋腻正反效应，然玉竹“补而不腻”，且从“滋味”、“效味”角度均不能阐明其机制。本项目基于甘的本质，提出“凡可启动或增强甜味信号的物质，均为甘味”，以此构建并通过“信味”标定“甘味”的新方法，在此基础上结合前期实验，提出“玉竹多糖上调甜味受体，增强并通过甜味信号通路调节AQP表达、Na+-K+-ATP活性及胃肠激素的释放，发挥滋补、滋腻效应，挥发油、黄酮回调多糖对AQP、胃肠激素的作用，故玉竹总体呈现‘补而不腻’”的假说；采用qRT-PCR、WB、激光共聚焦等技术考察玉竹对肠道甜味受体、甜味信号下游蛋白、AQP、Na+-K+-ATP、胃肠激素的影响，从动物、细胞水平阐明其“补而不腻”机制及效应物质基础。本项目从甜味受体角度，同时阐明玉竹“滋补-滋腻-不腻”机制，为玉竹、补阴药、甘味药的功效阐释提供新思路，提升了“甘补”药性理论的阐释力，丰富并助推了五味理论的传承与发展。

The Yin Tonics are sweet and have the positive and negative effects of “tonifying and cloying”, but the Polygonati Odorati Rhizoma presents “tonifying but not cloying” effect. However, basing on the current “taste-based flavor” and “effect-based flavor” theory, it is impossible to scientifically clarify the mechanism of “tonifying but not cloying” effect of Polygonati Odorati Rhizoma. Based on the essence of sweet, this project proposes that “Everything that can activate and enhance the sweet signal is sweet”, and builds the new method of calibrating “sweet” of traditional Chinese medicine through the “signaling pathway-based flavor”. On this basis and combined with previous experiments, this project put forward the hypothesis that “Odoratan could up-regulate the sweet receptors, and then regulate the expression of AQP and the activity of Na+-K+-ATP and mediates the release of gastrointestinal hormones by the sweet signaling pathway, which exhibited the effect of‘tonifying and cloying’. However the effects of odoratan on AQP and gastrointestinal hormones could be antagonized by the volatile oils and flavonoids of Polygonati Odorati Rhizoma. Therefore, Polygonati Odorati Rhizoma would generally present a ‘tonifying but not cloying’ effect.” In this study, qRT-PCR, WB and laser confocal technology will be used to investigate the effect of Polygonati Odorati Rhizoma on gut sweet receptors, AQP, Na+-K+-ATP, and gastrointestinal hormones. The mechanism and substantial basis of “tonifying but not cloying” will be clarified by these animal and cell experiments. This project is to research the mechanism of “tonifying but not cloying” effect of Polygonati Odorati Rhizoma from the perspective of sweet receptors in order to provide new ideas for the interpretation of the efficacy of Polygonati Odorati Rhizoma, Yin Tonics and sweet-taste traditional Chinese medicine. It will also improve the explanatory power of “Gan Bu” theory of TCM, and promote the inheritance and development of the five-flavor theories.